1. Field of the Invention
The present invention relates generally to the fields of medicine, pathology and molecular biology. More particularly, it concerns the involvement of miR function in the development of pathologic angiogenesis. Specifically, the invention relates to the antagonism of miR-23 and/or miR-27, and the agonism of miR-24, for treating AMD.
2. Description of Related Art
The growth of blood vessels through angiogenesis is a delicately controlled process which involves endothelial cell (EC) activation, proliferation, migration and maturation (Distler et al., 2003). Physiological angiogenesis is required for normal vascular development, as well as vascular homeostasis during adulthood. Pathological angiogenesis, commonly induced by tissue ischemia or inflammation, underlies numerous vascular disorders, such as age-related macular degeneration (AMD), a leading cause of blindness in the elderly Friedman (2004). Choroidal neovascularization (CNV), which involves abnormal growth of blood vessels in the back of the eye, is a hallmark of neovascular AMD (Jager et al. 2008). Although the pathogenic mechanisms underlying AMD are still largely unknown, vascular endothelial growth factor (VEGF) has been shown to play a causal role in the development of CNV (Grisanti & Tatar, 2008). Anti-VEGF agents have demonstrated efficacy in treating CNV in neovascular AMD (Brown et al., 2006; Rosenfeld et al., 2006), but have limited efficacy and potential side effects (Amrite et al., 2010; Zachary et al., 2005).
Recent studies have revealed important roles for microRNAs (miRNAs) in cardiovascular diseases and other disorders (Small & Olsen, 2011). miRNAs are small noncoding RNAs that negatively regulate gene expression by inducing mRNA degradation or inhibiting translation through binding to the 3′ untranslated region (3′UTR) of target mRNAs (Bartel, 2004). Often, miRNAs modulate broad collections of mRNAs encoding multiple components of complex biological pathways. Several miRNAs have been implicated in angiogenesis (Wang & Olsen, 2009; Urbich et al., 2008). A group of miRNAs has also been shown to be substantially decreased in a laser-induced CNV model (Shen et al., 2008). The significance of these miRNAs in AMD, however, remains to be formally established.